Variation in the frequencies of spontaneous and in vitro induced chromosome aberrations in human lymphocytes during natural and radiation-induced aging

The frequency of translocations detected by FISH in lymphocytes of control donors increases with age as a quadratic function. This process is faster in persons previously exposed to low doses of radiation. It means that translocation frequency can be used as a measure of biological age. Moreover, translocation frequency should be taken into account in biological reconstruction of absorbed doses. The frequencies of dicentrics detected by FIGH and FPG linearly increase with age in both groups, and this process occurs at equal rates during natural and radiation-induced aging. The age-dependent increase in the frequency of translocations exceeds the increase in dicentrics. The radiation sensitivity of lymphocytes estimated from the frequency of in vitro induced chromosomal aberrations tends to increase with age in the control group and decreases significantly in the group exposed to radiation; i.e., low-dose preexposure alters the pattern of the age dependence of radiation sensitivity in lymphocytes in vitro.     

Lethal and teratogenic effects after exposure to X-rays at various times of early murine gestation

Various well-defined stages during completion of the second meiotic division and early organogenesis of mouse embryos were X-irradiated with doses of 1-4 Gy (100-400 rad). The major risk was prenatal mortality with radiation sensitivity changing markedly with dependence on the developmental stage irradiated; in the case of day 1 even within hours. The surviving fetuses did show a significantly enhanced frequency of malformations on day 19 of gestation (mostly gastroschisis and some exencephalies). This was true for all stages between days 1 and 8; only sensitivity again changed considerably. The radiation doses used in this study are markedly higher than doses that can be expected from radiation diagnostics, but exposure is in a range comparable to doses that can occur in radiation therapy (e.g., Morbus Hodgkin).     

Dependence of microwave effect on the secondary structure of DNA on molecular weight of polynucleotide

The effect of ultralow power pulse-modulated electromagnetic radiation (average power density 60 microW/cm2, carrying frequency 1.05; 2.12; or 2.39 GHz; modulating pulses with frequency 4 Hz) on the secondary structure of DNA was investigated. It was established that the exposure of beta-alanine and formaldehyde containing aqueous DNA solution to electromagnetic radiation had activated the process of DNA despiralization under the action of beta-alanine--formaldehyde reaction product. The effect of electromagnetic radiation on the secondary structure of DNA can be removed by lowering of molecular weight of DNA to 0.46 x 10(6) (at carrying frequency 1.05 GHz), or to 0.25 x 10(3) (at carrying frequency 2.39 GHz).     

Experimental study of the plasma effect on the generation of microwave radiation in systems with a virtual cathode

Results are presented from experimental studies of the plasma effect on the generation of microwave radiation in systems with a virtual cathode. Using a triode with a virtual cathode as an example, it is shown that the cathode and anode plasmas reduce the generation efficiency; in particular, the power of the generated microwave radiation decreases and the radiation frequency and the microwave pulse duration change appreciably. It is demonstrated that, at high microwave powers, the power radiated into free space can be reduced by the plasma generated at the surface of the output window. This plasma appears due to discharges developing on the window surface under the combined action of bremsstrahlung, UV radiation, electrons and ions arriving from the beam formation zone, and the microwave electric field.     

Spectra of Electromagnetic Radiation from a Hot Plasma with Langmuir Turbulence in a Magnetic Field

A study is made of the generation of electromagnetic waves during the merging of two Langmuir plasmons in a hot plasma with a magnetic field. It is shown that the frequency of Langmuir plasmons can vary in the range from 0.8 to 1.1 of the electron Langmuir frequency. The spectrum and polarization of the emitted electromagnetic radiation are analyzed. It is found that the thermal motion of plasma particles may lead to the generation of electromagnetic waves in the frequency range from 1.6 to 2.2 of the electron Langmuir frequency. In a plasma with an isotropic Langmuir turbulence spectrum, the degree of circular polarization of the emitted radiation can amount to 50%.     

Radiation combines with immune checkpoint blockade to enhance T cell priming in a murine model of poorly immunogenic pancreatic cancer

Radiation has been a pillar of cancer therapy for decades. The effects of radiation on the anti-tumour immune response are variable across studies and have not been explicitly defined in poorly immunogenic tumour types. Here, we employed combination checkpoint blockade immunotherapy with stereotactic body radiation therapy and examined the effect on tumour growth and immune infiltrates in subcutaneous and orthotopic mouse models of pancreatic cancer. Although immune checkpoint blockade and radiation were ineffective alone, their combination produced a modest growth delay in both irradiated and non-irradiated tumours that corresponded with significant increases in CD8+ T cells, CD4+ T cells and tumour-specific T cells as identified by IFNγ ELISpot. We conclude that radiation enhances priming of tumour-specific T cells in poorly immunogenic tumours and that the frequency of these T cells can be further increased by combination with immune checkpoint blockade.     

Persistence of genetic damage in lymphocytes from former uranium miners

Lymphocytes from former uranium miners who finished work underground one or more decades ago were analysed with respect to possibly persisting genetic damage induced by their radiation exposure. A modified micronucleus-centromere test was used which determined the frequency of micronucleus-containing binucleate cells after cytochalasin B treatment and the percentage of centromere-free micronuclei, assessed with the help of immunofluorescence labeling of centromere protein B. Whereas the overall frequency of micronucleus-containing cells was not significantly elevated above the level found in a control group, former miners showed a greater percentage of centromere-free micronuclei, i.e. micronuclei containing only acentric fragments. Our results are in excellent agreement with those of an earlier uranium miner study and lend support to the assumption that genetic damage from alpha radiation can persist for many years after exposure, possibly due to genomic instability. The frequency of micronucleus-containing cells, but not the percentage of centromere-free micronuclei, significantly increased with time since last exposure in the mines. This can be attributed, at least in part, to the fact that miners who have finished working underground longer ago tend to be older, and there is an increase of the frequency of micronucleus-containing cells with age.     

The death-inducing effect and genomic instability

Exposure to ionizing radiation can induce a heritable change in the unirradiated progeny of irradiated cells. This non-targeted effect of ionizing radiation manifests as genomic instability, and although there is some debate as to the role of genomic instability in the carcinogenic process, it is thought by some to be an early step in radiation carcinogenesis. Although the mechanism of induction of genomic instability is not clearly understood, evidence suggests that secreted factors from irradiated cells may be involved. We have previously identified another non-targeted effect of ionizing radiation, the death-inducing effect. Exposure of unirradiated GM10115 cells to medium from chromosomally unstable clones was generally found to be cytotoxic. However, occasionally cells will survive in medium from unstable clones and can be clonally expanded. The absolute yield of survivors is independent of the initial number of cells plated when cell densities reached 5,000 or more cells/dish. After cytogenetic analysis of the surviving colonies, we found chromosomal instability in three of 40 clones analyzed, while some clones exhibited increased micronucleus frequency and HPRT mutation frequency. These data suggest that our chromosomally unstable GM10115 cells secrete factors that are cytotoxic to the majority of stable, parental cells but are also capable of inducing a heritable change in some of the survivors that can manifest as delayed genomic instability. These results suggest a mechanism whereby instability can be perpetuated through the influences of potentially cytotoxic factors produced by genomically unstable clones.     

G2 chromatid damage and repair kinetics in normal human fibroblast cells exposed to low- or high-LET radiation

Radiation-induced chromosome damage can be measured in interphase using the Premature Chromosome Condensation (PCC) technique. With the introduction of a new PCC technique using the potent phosphatase inhibitor calyculin-A, chromosomes can be condensed within five minutes, and it is now possible to examine the early damage induced by radiation. Using this method, it has been shown that high-LET radiation induces a higher frequency of chromatid breaks and a much higher frequency of isochromatid breaks than low-LET radiation. The kinetics of chromatid break rejoining consists of two exponential components representing a rapid and a slow time constant, which appears to be similar for low- and high-LET radiations. However, after high-LET radiation exposures, the rejoining process for isochromatid breaks influences the repair kinetics of chromatid-type breaks, and this plays an important role in the assessment of chromatid break rejoining in the G2 phase of the cell cycle.     

Radiobiological effects and medical applications of non-ionizing radiation

Radiation is used in medicine to diagnose and treat diseases but it can also cause harm to the body by burning or mutation. This depends on whether the radiation is ionizing or nonionizing. Despite its vast applications in surgery, dermatology and cosmetics, little is taught and thus known about non-ionizing radiation.This review article discusses the fundamentals of non-ionizing electromagnetic radiations. The main aim is to extensively explain the different types of non-ionizing radiation. This will equip students and medical personnel with knowledge on different medical applications and expose them to a variety of specializations in medicine that utilize non-ionizing radiation. The article discusses the physics, hazard, means of protection and medical application of each type of radiation: ultraviolet radiation, light (both visible light and LASER), infrared radiation, microwaves and extremely low frequency radiation separately. It presents these terms in a simple manner that avoids rigors mathematics and physics, which makes them comprehensible for medical students.The development of new diagnostic and therapeutic approaches could also lead to increased hazards to the body unless they are treated with precaution. If not adequately monitored, a significant health risk may be posed to potentially exposed employees. Hence proper dosage should be used for non-ionizing radiation. This is only possible through understanding of the risks/benefits of these radiations by studying the physics and radiobiological effects of each individual radiation.     

Randomness of base substitution mutations induced in the lacI gene of Escherichia coli by ionizing radiation

The lacI system of Escherichia coli provides a method for monitoring mutational events at a large number of sites. Using this system, we have previously determined the mutational spectra for gamma-ray and beta-particle emissions resulting from the decay of tritium. Analysis of these mutational spectra reveals that base substitution mutations induced by ionizing radiation are distributed nearly randomly throughout the lacI gene and include all detectable substitution events. The distribution of ionizing radiation-induced mutagenesis is similar to the low frequency of occurrence mutational events induced by other SOS-dependent mutagens. The lack of an apparent nonrandom or high frequency of occurrence component seen with other SOS-dependent mutagens can be best explained as the result of the random interaction of ionizing radiation with the DNA bases leading to production of a variety of base substitutions.     

Status of hemapoiesis in residents of the Techa riverside villages in the period of maximum radiation exposure. Report 2. Influence of exposure dose and dose rate of red bone marrow as well as modifying factors on the frequency of cytopenia and cytosis

The purpose of this study is a retrospective estimation of the influence of dose and dose rate of the red bone marrow chronic radiation exposure in combination with various modifying factors (gender, age, comorbidity) on the frequency of deviations from normal values of the results of peripheral blood investigation in humans exposed on the Techa River. The results of investigation show that humans chronically exposed to radiation can develop marked changes in the cellular composition of peripheral blood characterized by a tendency to cytopenia (signs of the decompensation of hemopoiesis). The tendency to cytopenia can be identified earlier in the lymphoid germ, and later in platelet and erythroid lines. A high lability of granulocytes under the influence of various, often infectious, factors is the cause of the lack of statistically significant differences in terms of frequency of neutropenia. Several non-radiation factors (gender, age, health status) in combination with radiation exposure could have a modifying influence on hematopoiesis, which contributed to the disruption of adaptation processes and the development of conditions characterized by a tendency to cytopenias in exposed individuals. The red bone marrow dose rate reduction resulted in a gradual decrease in the frequency of erythrocytopenia, thrombocytopenia, neutropenia and lymphocytopenia in the group of exposed population. Increased frequencies of erythrocytosis, thrombocytosis, lymphocytosis, monocytosis and neutrophilia were observed when the median dose rate was reduced to the level of 0.024 Gy/year (in the year 1956), which could be regarded as activation of regenerative processes in hematopoiesis.     

Dipole Mechanism Generation of Terahertz Waves under Laser-Cluster Interaction

The feasibility of dipole radiation of terahertz waves under the action of a femtosecond laser pulse on a cluster is demonstrated theoretically. It is shown that the dipole mechanism of terahertz radiation generation plays a decisive role in the interaction of a laser pulse with small-size clusters with a sufficiently high electron collision frequency. The dependences of the spectral, angular, energetic, and spatiotemporal characteristics of the terahertz signal on the density of free electrons in the cluster plasma under the conditions in which dipole radiation is dominant are investigated. It is shown that the energy of terahertz radiation is maximal under the resonance conditions, when the laser frequency coincides with the eigenfrequency of a spherical cluster.     

Dose dependence for radiation-induced allelic recombination in Chlamydomonas reinhardi

The frequency of recombination between the acetate 14A and E alleles of the green alga Chlamydomonas reinhardi can be changed by γ radiation only if germinating zygospores are irradiated during one or other of two short meiotic stages. During the first, which is probably located in preleptotene, the frequency of allelic recombination increased linearly with dose and at 20.3 krad, the highest dose used, recombination frequency was increased by a factor of 7 while zygospore survival was reduced to 58%. During the second stage, probably located in late zygotene or early pachytene, a maximum increase of 1.5–2 times the control frequency was found at doses between 2 and 5 krad, higher doses producing no further increase.

The spontaneous recombination frequencies in zygospores from two different crosses, obtained by mating two different acetate 14A strains to a common acetate 14E stock, differed by a factor of about 10, suggesting that the acetate 14A strains possess different alleles of at least one “recombination” gene. In absolute terms, the cross which had a high spontaneous frequency exhibited a larger response to radiation, particularly at the second stage, though as a proportion of the control frequency the response was smaller. Zygospores of the second cross were also more sensitive to the lethal effects of the radiation.     

Lactate-mediated changes in growth morphology and transformation frequency of irradiated C3H 10T1/2 cells

Treatment of mammalian cells with lactate or inhibitors of glycolysis alters their radiation response, particularly in the low dose region of the dose response curve. The occurrence of both high lactate levels and high glycolytic metabolism in tumours is well known and therefore the effect of lactate on a cell line sensitive to radiation induced transformation was examined using a single exposure to Cobalt 60 gamma rays as the carcinogen challenge. The results indicate that cells treated with 5mM lactate before irradiation exhibit changes in morphology and growth rate and that the transformation frequency is increased by three to ten fold following 24 hours lactate treatment just prior to irradiation. Examination of radiation survival curves showed a positive correlation between transformation frequency and size of the shoulder, but increasing transformation frequency was associated with a decrease in Do. A mechanism involving altered Redox potential in lactate treated cells is suggested. The results are discussed in terms of their possible significance for radiotherapy.     

Beta-radiation-induced resistance to MNNG initiation of papilloma but not carcinoma formation in mouse skin

We have shown previously that the risk of tumor initiation, promotion, and progression in animals initiated with alkylating agents can be drastically altered by hyperthermia treatments. We show here that ionizing radiation can also alter the risk of tumor initiation by alkylating agents. Using a two-step skin tumorigenesis protocol in female SENCAR mice (initiation by MNNG, promotion with TPA), we exposed the dorsal skin of the mice to various doses of 90Sr/90Y beta radiation near the time of initiation. The radiation produced a dose-dependent reduction in the number of papillomas which appeared after TPA promotion, with about a 20% reduction in animals receiving 0.5 Gy surface dose just before initiation, about 50% reduction after 2.5 Gy, and greater than 80% at doses above 5 Gy. A dose of 2.5 Gy in animals initiated with DMBA produced no significant reduction. One skin hyperthermia treatment (44 degrees C, 30 min) along with radiation in MNNG-initiated animals partially blocked the protective effect of radiation and increased the papilloma frequency. Radiation (2.5 Gy) given either 6 days before or after MNNG initiation was less effective but still reduced papilloma frequency about 20%. In sharp contrast to the marked reduction in papilloma formation, these same animals showed no change in carcinoma frequency with any of the doses or schedules of beta radiation. MNNG initiation alone produced three types of initiated cells. One type, produced in low yield, was promotion-independent with a high probability of progression to a carcinoma and appeared unaffected by the radiation. A second type, produced in intermediate yield, was promotion-dependent and also had a high progression probability, but was likewise unaffected by the radiation. The third and most abundant type was promotion-dependent with a very low progression probability. Radiation exposure resulted in a decrease in the risk of an MNNG initiation event which led only to the third type of cell. The data therefore indicate that the risk of some, but not all, tumor-initiating events caused by alkylating agents can be reduced by an exposure to ionizing radiation.     

Effects of 100 GHz radiation on alkaline phosphatase activity and antigen–antibody interaction

Equipment that generates microwave radiation (MWR) spanning the frequency range of 300 MHz–100 GHz is becoming more common. While MWR lacks sufficient energy to break chemical bonds, the disagreement as to whether MWR exposure is detrimental to cellular dysfunction may be difficult to clarify using complex systems such as whole animals, cells, or cell extracts. Recently, the high frequency range of terahertz (THz) radiation has been explored and sources of radiation and its detectors have been developed. THz radiation is associated with the frequency interval from 100 GHz to 20 THz and constitutes the next frontier in imaging science and technology. In the present study, we investigated the effect of radiation in the low frequency THz range (100 GHz) on two defined molecular interactions. First, the interaction of soluble or immobilized calf alkaline phosphatase with the substrate p‐nitrophenylphosphate and second, the interaction between an antibody (mouse monoclonal anti‐DNP) and its antigen (DNP). Irradiation of enzyme either prior to addition of substrate or during the enzymatic reaction resulted in small but significant reductions in enzyme activity. These differences were not observed if the enzyme had previously been immobilized onto plastic microwells. Exposure of immobilized antigen to radiation did not influence the ability of the antigen to interact with antibody. However, irradiation appeared to decrease the stability of previously formed antigen–antibody complexes. Our data suggest that 100 GHz radiation can induce small but statistically significant alterations in the characteristics of these two types of biomolecular interactions. Bioelectromagnetics 30:167–175, 2009. © 2008 Wiley‐Liss, Inc.     

Elevated Frequency of Cataracts in Birds from Chernobyl

Background

Radiation cataracts develop as a consequence of the effects of ionizing radiation on the development of the lens of the eye with an opaque lens reducing or eliminating the ability to see. Therefore, we would expect cataracts to be associated with reduced fitness in free-living animals.

Methodology/Principal Findings

We investigated the incidence of lens opacities typical of cataracts in more than 1100 free-living birds in the Chernobyl region in relation to background radiation. The incidence of cataracts increased with level of background radiation both in analyses based on a dichotomous score and in analyses of continuous scores of intensity of cataracts. The odds ratio per unit change in the regressor was 0.722 (95% CI 0.648, 0.804), which was less than odds ratios from investigations of radiation cataracts in humans. The relatively small odds ratio may be due to increased mortality in birds with cataracts. We found a stronger negative relationship between bird abundance and background radiation when the frequency of cataracts was higher, but also a direct effect of radiation on abundance, suggesting that radiation indirectly affects abundance negatively through an increase in the frequency of cataracts in bird populations, but also through direct effects of radiation on other diseases, food abundance and interactions with other species. There was no increase in incidence of cataracts with increasing age, suggesting that yearlings and older individuals were similarly affected as is typical of radiation cataract.

Conclusions/Significance

These findings suggest that cataracts are an under-estimated cause of morbidity in free-living birds and, by inference, other vertebrates in areas contaminated with radioactive materials.